For years clinicians have known that people engulfed in misery become ill. Studies of bereavement, other high stress life events, and depression have shown that affected individuals more frequently become ill with and die of many types of illness, including infections, cardiovascular disease, autoimmune disease, allergies and cancer. Recent investigations into these clinical observations have in part focused on the immune system. Bereaved individuals have impaired cellular immunity apparently not mediated by several measured neurohormones. Altered immune cell function has been reported in patients with major depression when compared to normal control subjects. It is unclear whether these changes in cell function are mediated by neurohormones. It is also unclear if these changes are related to life events stress as compared to depression. The possibility of using altered immune cell functions as markers of depression has not been explored. The proposed research would provide within subjects longitudinal follow-up of depressed patients through relapse and remission, and group comparisons between depressed patients and control subjects, and enable correlational analyses among relevant immunologic, behavioral and neuroendocrine variables. Few previous studies have examined these three areas simultaneously. The immune measures are: 1) monoclonal antibody labeling and FACS counting of lymphocytes, 2) T cell blastogenesis in response to stimulation by PHA and Con A; 3) production of IL-2 by cells stimulated by PHA; and 4) allostimulated antigen dependent cytotoxic T cell activity. The behavioral variables include the life events stress level, as assessed using the PERI-M, and the severity of depression as measured by both the Beck Depression Inventory and the Hamilton Rating Scale for Depression. In addition, medical health will be evaluated longitudinally with the Interval Medical History. The plasma neurohormones measured are cortisol, ACTH, beta-endorphin, growth hormone and prolactin. Also, a dexamethasone suppression test (DST) and 24-hour urinary free cortisol will be used to evaluate the subjects' neuroendocrine status. Secondly, we will search for biological state markers of major depression by examining the individual, or combinations of, the measures of immune cell function and neurohormones, at inclusion of the patients in the study and at times of relapse and remission. It is hoped that the results of these studies will provide initial information on the mechanism of immune cell alterations associated with major depression or severe life events stress.